Molecular mechanisms of Streptococcus pneumoniae-targeted autophagy via pneumolysin, Golgi-resident Rab41, and Nedd4-1-mediated K63-linked ubiquitination

Michinaga Ogawa*, Ryuta Matsuda, Naoki Takada, Mikado Tomokiyo, Shouji Yamamoto, Sayaka Shizukusihi, Toshiyuki Yamaji, Yuko Yoshikawa, Mitsutaka Yoshida, Isei Tanida, Masato Koike, Miyo Murai, Hidetoshi Morita, Haruko Takeyama, Akihide Ryo, Jun Lin Guan, Masahiro Yamamoto, Jun ichiro Inoue, Toru Yanagawa, Mitsunori FukudaHiroshi Kawabe, Makoto Ohnishi

*この研究の対応する著者

研究成果査読

14 被引用数 (Scopus)

抄録

Streptococcus pneumoniae is the most common causative agent of community-acquired pneumonia and can penetrate epithelial barriers to enter the bloodstream and brain. We investigated intracellular fates of S. pneumoniae and found that the pathogen is entrapped by selective autophagy in pneumolysin- and ubiquitin-p62-LC3 cargo-dependent manners. Importantly, following induction of autophagy, Rab41 was relocated from the Golgi apparatus to S. pneumoniae-containing autophagic vesicles (PcAV), which were only formed in the presence of Rab41-positive intact Golgi apparatuses. Moreover, subsequent localization and regulation of K48- and K63-linked polyubiquitin chains in and on PcAV were clearly distinguishable from each other. Finally, we found that E3 ligase Nedd4-1 was recruited to PcAV and played a pivotal role in K63-linked polyubiquitin chain (K63Ub) generation on PcAV, promotion of PcAV formation, and elimination of intracellular S. pneumoniae. These findings suggest that Nedd4-1-mediated K63Ub deposition on PcAV acts as a scaffold for PcAV biogenesis and efficient elimination of host cell-invaded pneumococci.

本文言語English
論文番号e12846
ジャーナルCellular Microbiology
20
8
DOI
出版ステータスPublished - 2018 8

ASJC Scopus subject areas

  • 微生物学
  • 免疫学
  • ウイルス学

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